Jun 9, 2017

Hypoxia-induced DNA demethylation allows Human Pluripotent Cell-Derived Neural Precursor Cells to differentiate into astrocytes
Published in Stem Cell Reports

Human neural precursor cells (hNPCs) derived from pluripotent stem cells can rapidly differentiate into neurons with high efficiency, but they require long-term culturing to differentiate efficiently into astrocytes. The mechanisms underlying this biased fate specification of hNPCs remain elusive. Our member, Dr. Nakashima showed that hypoxia confers astrocytic differentiation potential on hNPCs through epigenetic gene regulation, and that this was achieved by cooperation between hypoxia-inducible factor 1a and Notch signaling, accompanied by a reduction of DNA methylation level in the promoter region of a typical astrocyte-specific gene, Glial fibrillary acidic protein. Furthermore, they found that this hypoxic culture condition could be applied to rapid generation of astrocytes from Rett syndrome patient-derived hNPCs, and that these astrocytes impaired neuronal development.

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Yasui T, Uezono N, Nakashima H, Noguchi H, Matsuda T, Noda-Andoh T, Okano H, Nakashima K.
Hypoxia Epigenetically Confers Astrocytic Differentiation Potential on Human Pluripotent Cell-Derived Neural Precursor Cells.
Stem Cell Reports. 2017 Jun 6;8(6):1743-1756.